Effect of randomized serum progesterone concentration on secretory endometrial histologic development and gene expression

Young, Steven L.; Savaris, Ricardo Francalacci; Lessey, Bruce A.; Sharkey, Andrew; Balthazar, Ursula; Zaino, Richard J.; Sherwin, Robert A.; Fritz, Marc A.

doi:10.1093/humrep/dex252

Cited by 45 publications

(31 citation statements)

References 23 publications

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“…Morphological delay was observed in the group supplemented with lower P concentrations. Higher P levels resulted in normal histology but aberrant gene expression [20]. This experimental trial supports the clinical study of Yovich et al, which reported that the likelihood of pregnancy in cryopreserved embryo transfer cycles under hormonal control is highly dependent on the circulating concentration of P, with an optimal P concentration of 70–99 nmol/l after vaginal administration [9].…”

Section: Discussionsupporting

confidence: 77%

Measuring the serum progesterone level on the day of transfer can be an additional tool to maximize ongoing pregnancies in single euploid frozen blastocyst transfers

Boynukalın

Gültomruk

Turgut

et al. 2019

Reprod Biol Endocrinol

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BackgroundEndometrial preparation with hormone replacement therapy (HRT) is the preferred regimen for clinicians due to the opportunity to schedule the day of embryo transfer and for patients due to the requirement of fewer visits for frozen-warmed embryo transfers (FET). The increasing number of FETs raises the question of the serum P levels required to optimize the pregnancy outcome on the embryo transfer day.MethodsThis prospective cohort study includes patients who underwent single euploid FET. All patients received HRT with oestradiol valerate (EV) and 100 mg of intramuscular (IM) progesterone (P). FET was scheduled 117–120 h after the first IM administration of 100 mg P. The serum P level was analyzed 1 h before the embryo transfer (ET). In all cycles, only embryos that were biopsied on day 5 were utilized for FET. Next generation sequencing (NGS) was used for comprehensive chromosomal analysis.ResultsOverall, the ongoing pregnancy rate (OPR) was 58.9% (99/168). Data were then categorized according to the presence (Group I; n = 99) or the absence (Group II; n = 69) of an ongoing pregnancy. No significant differences regarding, female age, body mass index (BMI), number of previous miscarriages, number of previous live birth, sperm concentration, number of oocytes retrieved, number of mature oocytes (MII), rate of fertilized oocytes with two pronuclei (2PN), trophectoderm score, inner cell mass (ICM) score, endometrial thickness (mm), oestrodiol (E2) and P levels prior to IM P administration were found between two groups. The P levels on the day of ET (ng/ml) were significantly higher in Group I (28 (5.6–76.4) vs 16.4 (7.4–60) p = 0.039). The P level on the day of ET was a predictor of a higher OPR (p < 0.001 OR: 1.033 95%CI [1.009–1.056]) after multivariate analysis. The ROC curve showed a significant predictive value of serum P levels on the day of ET for OPR, with an AUC (95%CI) = 0.716 (0.637–0.795). The optimal cut-off value for prediction of the OPR was a P level of 20.6 ng/ml (71.7% sensitivity, 56.5% specificity).ConclusionsThe present study suggests a minimum threshold of the serum P value on the day of ET that needs to be reached in HRT cycles to optimize the clinical outcome. Individualization of the P dosage should be evaluated in further studies.

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Section: Discussionsupporting

confidence: 77%

Measuring the serum progesterone level on the day of transfer can be an additional tool to maximize ongoing pregnancies in single euploid frozen blastocyst transfers

Boynukalın

Gültomruk

Turgut

et al. 2019

Reprod Biol Endocrinol

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“…Thus, it seems that P resistance is not the same as P deficiency. Normal endometrium seems so robust in its ability to respond to P that endometrial histology was unchanged across a wide range of concentrations, with delayed histologic changes only seen with P concentrations below those seen in ovulatory women-although only a small number of genes showed a significant dose-response (59) (Fig. 1).…”

Section: Progesterone Action and Implantationmentioning

confidence: 99%

“…It was shown to be reduced when histology was delayed, but more importantly, when histology was ''in phase'' with b3 integrin expression expected, this integrin was lacking in clinical conditions associated with infertility, including endometriosis (76) and hydrosalpinges (77), and aberrantly expressed in a significant subset of women with unexplained infertility (78) and unexplained recurrent pregnancy loss (79). The return of normal fertility and integrin expression was demonstrated using salpingectomy (80) or treatment with an aromatase inhibitor (59). Interestingly, anb3 integrin expression is tied to the downregulation of E receptor-a, which is seen in both LPD and endometriosis.…”

Section: Endometrial Assessmentmentioning

confidence: 99%

What exactly is endometrial receptivity?

Lessey

Young

2019

Fertility and Sterility

Self Cite

267

166

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Endometrial receptivity is a complex process that provides the embryo with the opportunity to attach, invade, and develop, culminating in a new individual and continuation of the species. The window of implantation extends 3-6 days within the secretory phase in most normal women. In certain inflammatory or anatomic conditions, this window is narrowed or shifted to preclude normal implantation, leading to infertility or pregnancy loss. Of the factors that prevent normal implantation and pregnancy, embryo and endometrial quality share responsibility. In this review, we highlight the advances in the study of implantation from the perspective of the endometrium, normally a barrier to implantation. New advances will allow the early identification of defects in endometrial receptivity and provide new avenues for treatment that promote successful establishment of pregnancy.

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“…24 Normal histological maturation has been demonstrated in response to very low blood levels of progesterone. 25 However, targeted gene expression analysis showed a dose-response pattern for some genes with increasing progesterone concentrations, 25 suggesting that a pre-receptive result with the ERA test corresponds to a low plasma progesterone level.…”

Section: Introductionmentioning

confidence: 99%

Are different markers of endometrial receptivity telling us different things about endometrial function?

Saxtorph

Persson

Hallager

et al. 2020

American J Rep Immunol

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Problem: To what extent do endocrine, immunological, gene expression and histological markers of endometrial receptivity correlate? Method of study: Between November 2017 and September 2019, 121 women referred to a University Hospitals Fertility Clinic consented to inclusion in this cohort study. The women underwent timed endometrial biopsy followed by blood samples in a hormone-substituted cycle. Of these, 37 women had just started IVF treatment, and the remaining 84 had experienced recurrent implantation failure following IVF/ ICSI. The hormone-substituted cycle consisted of initiation with oral oestradiol followed by addition of vaginal progesterone treatment for five full days. Endometrial biopsies were subject to histological examination, immune cell markers by immunohistochemistry (CD56 + , CD16 + , CD163 + , FoxP3) and gene expression microarray analyses with the endometrial receptivity array (ERA ®) test (Igenomix). Plasma progesterone and oestradiol were measured on the day of biopsy. Results: CD56 + uterine natural killer (uNK) cell counts correlate with transcriptional markers of endometrial receptivity assessed by the ERA test. Endometrial maturation, receptivity and immunological markers were not correlated with mid-luteal blood plasma progesterone level. Mid-luteal serum oestradiol level correlated with markers of endometrial maturation and receptivity. The tests were carried out during a standard hormone substitution cycle, and the findings may not apply in the natural cycle. Conclusion: CD56 + uNK cell counts and endometrial receptivity assessed by the ERA test appear to be linked. Mid-luteal progesterone levels were not correlated to the tested markers of endometrial receptivity. In contrast, mid-luteal oestradiol level was inversely related to markers of endometrial receptivity and maturation.

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Effect of randomized serum progesterone concentration on secretory endometrial histologic development and gene expression

Cited by 45 publications

References 23 publications

Measuring the serum progesterone level on the day of transfer can be an additional tool to maximize ongoing pregnancies in single euploid frozen blastocyst transfers

Measuring the serum progesterone level on the day of transfer can be an additional tool to maximize ongoing pregnancies in single euploid frozen blastocyst transfers

What exactly is endometrial receptivity?

Are different markers of endometrial receptivity telling us different things about endometrial function?

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